High-Coverage Four-Dimensional Data-Independent Acquisition Proteomics and Phosphoproteomics Enabled by Deep Learning-Driven Multidimensional Predictions.

Four-dimensional (4D) data-independent acquisition (DIA)-based proteomics is a promising technology. However, its full performance is restricted by the time-consuming building and limited coverage of a project-specific experimental library. Herein, we developed a versatile multifunctional deep learning model Deep4D based on self-attention that could predict the collisional cross section, retention time, fragment ion intensity, and charge state with high accuracies for both the unmodified and phosphorylated peptides and thus established the complete workflows for high-coverage 4D DIA proteomics and phosphoproteomics based on multidimensional predictions. A 4D predicted library containing ∼2 million peptides was established that could realize experimental library-free DIA analysis, and 33% more proteins were identified than using an experimental library of single-shot measurement in the example of HeLa cells. These results show the great values of the convenient high-coverage 4D DIA proteomics methods.

Genetic analysis and QTL mapping for silique density in rapeseed (Brassica napus L.).

KEY MESSAGE: Genetic models, QTLs and candidate gene for silique density on main inflorescence of rapeseed were identified. Silique density is one of the critical factors to determine seed yield and plant architecture in rapeseed (Brassica napus L.); however, the genetic control of this trait is largely unknown. In this study, the genetic model for silique density on main inflorescence (SDMI) of rapeseed was estimated according to the phenotypic data of P1 (an inbreed line with high SDMI), P2 (an inbreed line with low SDMI), F1, F2, BC1P1 and BC1P2 populations, revealing that SDMI is probably controlled by multi-minor genes with or without major gene. The QTLs for SDMI and its component characters including silique number on main inflorescence (SNMI) and main inflorescence length (MIL) were consequently mapped from a DH population derived from P1 and P2 by using a genetic linkage map constructed by restriction site-associated DNA sequencing (RAD seq) technology. A total of eight, 14 and three QTLs were identified for SDMI, SNMI and MIL under three environments, respectively, with an overlap among SDMI and SNMI in 55.7-75.4 cm on linkage group C06 which corresponding to 11.6-27.3 Mb on chromosome C06. Genomic resequencing was further conducted between a high- and a low-SDMI pool constructed from the DH population, and QTL-seq analysis identified a 0.15 Mb interval (25.98-26.13 Mb) from the C06-QTL region aforementioned. Transcriptome sequencing and qRT-PCR identified one possible candidate gene (BnARGOS) from the 0.15 Mb interval. This study will provide novel insights into the genetic basis of SD in rapeseed.

Transcriptome profiling reveals multiple regulatory pathways of Tamarix chinensis in response to salt stress.

KEY MESSAGE: Multiple regulatory pathways of T. chinensis to salt stress were identified through transcriptome data analysis. Tamarix chinensis (Tamarix chinensis Lour.) is a typical halophyte capable of completing its life cycle in soils with medium to high salinity. However, the mechanisms underlying its resistance to high salt stress are still largely unclear. In this study, transcriptome profiling analyses in different organs of T. chinensis plants in response to salt stress were carried out. A total number of 2280, 689, and 489 differentially expressed genes (DEGs) were, respectively, identified in roots, stems, and leaves, with more DEGs detected in roots than in stems and leaves. Gene Ontology (GO) term analysis revealed that they were significantly enriched in "biological processes" and "molecular functions". Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that "Beta-alanine metabolism" was the most differentially enriched pathway in roots, stems, and leaves. In pair-to-pair comparison of the most differentially enriched pathways, a total of 14 pathways, including 5 pathways in roots and leaves, 6 pathways in roots and stems, and 3 pathways in leaves and stems, were identified. Furthermore, genes encoding transcription factor, such as bHLH, bZIP, HD-Zip, MYB, NAC, WRKY, and genes associated with oxidative stress, starch and sucrose metabolism, and ion homeostasis, were differentially expressed with distinct organ specificity in roots, stems, and leaves. Our findings in this research provide a novel approach for exploring the salt tolerance mechanism of halophytes and identifying new gene targets for the genetic breeding of new plant cultivars with improved resistance to salt stress.

Assessing food safety risks based on a geospatial analysis: toward a cross-regional food safety management.

BACKGROUND: Food safety risks (FSRs) are increasingly characterized by geographical complexity along with rapid urbanization, changing dietary pattern, and the modernization of the food industry. These factors pose challenges for food risk control in developing economies, more so during the global COVID-19 pandemic. The accurate assessment of risk source and transfer path is a crucial step toward enhancing cross-regional food safety management. This study aims to examine the spatial distribution, transfer path and driving factors of FSRs in China, provided with a national food safety database collected from 8.63 million batches of food sampling inspections for 33 different types of foods across 30 provinces. RESULTS: The findings reveal significant regional disparities in FSRs, which is the highest in the west with small-scale sampling inspection and the lowest in the east with intensive sampling inspection. Catering and processed foods with higher daily consumption suffer more profound FSR than agricultural products. As evidenced by the shrinking low-low agglomeration areas, the local FSRs have been effectively controlled. The high-high agglomeration areas playing positive impacts on risk control are expanding while distributed discretely. CONCLUSION: The spatial transfer of FSRs is significantly driven by multiple drivers: regulatory capacity and intensity, information disclosure, food industry, regional economy, and food consumption. Assessing FSRs based on a geospatial analysis contributes to identifying risk sources, optimizing risk management, and constructing a sustainable food safety system. © 2023 Society of Chemical Industry.

High-Throughput Nano-Electrostatic-Spray Ionization/Photoreaction Mass Spectrometric Platform for the Discovery of Visible-Light-Activated Photocatalytic Reactions in the Picomole Scale.

Visible-light-activated photocatalysis has emerged as a green and powerful tool for the synthesis of various organic compounds under mild conditions. However, the expeditious discovery of novel photocatalysts and synthetic pathways remains challenging. Here, we developed a bifunctional platform that enabled the high-throughput discovery and optimization of new photochemical reactions down to the picomole scale. This platform was designed based on a contactless nano-electrostatic-spray ionization technique, which allows synchronized photoreactions and high-throughput in situ mass spectrometric analysis with a near-100% duty cycle. Using this platform, we realized the rapid screening of photocatalytic reactions in ambient conditions with a high speed of less than 1.5 min/reaction using picomolar materials. The versatility was validated by multiple visible-light-induced photocatalytic reactions, especially the discovery of aerobic C-H thiolation with low-cost organic photocatalysts without any other additives. This study provided a new paradigm for the integration of ambient ionization techniques and new insights into photocatalytic reaction screening, which will have broad applications in the development of new visible-light-promoted reactions.

Long non-coding RNA AGER-1 functionally upregulates the innate immunity gene AGER and approximates its anti-tumor effect in lung cancer.

Little is known about long non-coding RNA (lncRNA) related to innate immunity in lung cancer. The advanced glycosylation end-product specific receptor (AGER) belongs to the immunoglobulin superfamily, and currently, is the only innate immune pattern-recognition receptor whose abnormal expression has been detected in lung cancer. We aimed to explore the lncRNA that is related to AGER and test its effect on lung carcinogenesis. We selected one lncRNA whose chromosome location is in close proximity to AGER namely lnc-AGER-1 (defined as lncAGER). The expression of lncAGER was tested in 276 pairs of lung cancer tissues and adjacent lung normal tissues, and its correlation with lung cancer clinical progress was analyzed. A series of assays were further used to assess the biological function of lncAGER on lung cancer development, tumor immunity and autophagy. LncAGER expression was moderately correlated with AGER expression (r = 0.360, P = 2.15 × 10-18 ) underlying a mechanism that lncAGER upregulates AGER by competitively binding to miRNA-185. LncAGER was significantly down-regulated in 76.4% of lung cancer tissues compared to adjacent normal tissues due to promoter hypermethylation. Over-expression of the lncRNA resulted in significant decreases in proliferation rate, migration ability, colony formation efficiency of lung cancer cells and tumor growth in nude mice. Notably, lncAGER possibly conduced to enhancement of cytotoxic effect of THP1. Additionally, the lncRNA also promoted cell apoptosis by strengthening autophagy. Taken together, these observations suggest that lncAGER has an inhibitory effect on lung cancer development via AGER, which may serve as a target for lung cancer treatment.

The Effects of Exogenous 2,4-Epibrassinolide on the Germination of Cucumber Seeds under NaHCO3 Stress.

This investigation focused on the suppressive impact of varying NaHCO3 concentrations on cucumber seed germination and the ameliorative effects of 2,4-Epibrassinolide (EBR). The findings revealed a negative correlation between NaHCO3 concentration and cucumber seed germination, with increased NaHCO3 concentrations leading to a notable decline in germination. Crucially, the application of exogenous EBR significantly counteracted this inhibition, effectively enhancing germination rates and seed vigor. Exogenous EBR was observed to substantially elevate the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), thereby mitigating oxidative damage triggered under NaHCO3 stress conditions. Additionally, EBR improved enzyme activity under alkaline stress conditions and reduced starch content in the seeds. Pertinently, EBR upregulated genes that were associated with gibberellin (GA) synthesis (GA20ox and GA3ox), and downregulated genes that were linked to abscisic acid (ABA) synthesis (NCED1 and NCED2). This led to an elevation in GA3 concentration and a reduction in ABA concentration within the cucumber seeds. Therefore, this study elucidates that alleviating oxidative stress, promoting starch catabolism, and regulating the GA and ABA balance are key mechanisms through which exogenous EBR mitigates the suppression of cucumber seed germination resulting from alkaline stress.

Study on the Applications and Regulatory Mechanisms of Grafting on Vegetables.

Grafting can overcome problems with soil sensitivity, enhance plant stress tolerance, improve product quality, and increase crop yield and value. This paper reviews the various mechanisms of vegetable grafting, the graft survival process and its influencing factors, the practical applications of grafting, and the molecular regulation of grafting in vegetables. The importance of germplasm and rootstock interactions, the mechanization of vegetable grafting, and future aspects, including intelligence and digitalization, are discussed.

Ultra-high-throughput mapping of the chemical space of asymmetric catalysis enables accelerated reaction discovery.

The discovery of highly enantioselective catalysts and elucidating their generality face great challenges due to the complex multidimensional chemical space of asymmetric catalysis and inefficient screening methods. Here, we develop a general strategy for ultra-high-throughput mapping of the chemical space of asymmetric catalysis by escaping the time-consuming chiral chromatography separation. The ultrafast ( ~ 1000 reactions/day) and accurate (median error < ±1%) analysis of enantiomeric excess are achieved through the ion mobility-mass spectrometry combines with the diastereoisomerization strategy. A workflow for accelerated asymmetric reaction screening is established and verified by mapping the large-scale chemical space of more than 1600 reactions of α-asymmetric alkylation of aldehyde with organocatalysis and photocatalysis. Importantly, a class of high-enantioselectivity primary amine organocatalysts of 1,2-diphenylethane-1,2-diamine-based sulfonamides is discovered by the accelerated screening, and the mechanism for high-selectivity is demonstrated by computational chemistry. This study provides a practical and robust solution for large-scale screening and discovery of asymmetric reactions.

Influence of Loss Aversion and Income Effect on Consumer Food Choice for Food Safety and Quality Labels.

Food safety and food quality are two closely related aspects of the food management system. The difference between the two is that one keeps consumers safe while the other keeps consumers satisfied. This study examined the differences in how consumers value food safety and food quality with a focus on the influence of loss aversion on one's psychological level and of income effect on one's socio-demographic level. Our findings indicate that loss aversion and income effect significantly influence the way consumers value food safety vs. quality labels when considering potential health risks and food price. High risk-averse and low-income consumers with strong loss aversion and a weak income effect show a higher demand for food safety labels as a way to ensure easy access to safety indications. Low risk-averse and high-income consumers with weak loss aversion and a strong income effect show a higher demand for food quality labels because they hope to gain more health benefits from high-quality food at good prices. This study provides insights that will assist public authorities and food industry in balancing food safety control and food quality improvement in order to meet the heterogeneous market demand changing alongside the transition of China's food consumption and production.

Distinct lipid metabolic dysregulation in asymptomatic COVID-19.

Asymptomatic infection is a big challenge in curbing the spread of COVID-19. However, its identification and pathogenesis elucidation remain issues. Here, by performing comprehensive lipidomic characterization of serum samples from 89 asymptomatic COVID-19 patients and 178 healthy controls, we screened out a panel of 15 key lipids that could accurately identify asymptomatic patients using a new ensemble learning model based on stacking strategy with a voting algorithm. This strategy provided a high accuracy of 96.0% with only 3.6% false positive rate and 4.8% false negative rate. More importantly, the unique lipid metabolic dysregulation was revealed, especially the enhanced synthesis of membrane phospholipids, altered sphingolipids homeostasis, and differential fatty acids metabolic pattern, implicating the specific host immune, inflammatory, and antiviral responses in asymptomatic COVID-19. This study provides a potential prediagnostic method for asymptomatic COVID-19 and molecular clues for the pathogenesis and therapy of this disease.

Effects of gut microbiota and probiotics on Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with high morbidity, disability, and fatality rate, significantly increasing the global burden of public health. The failure in drug discovery over the past decades has stressed the urgency and importance of seeking new perspectives. Recently, gut microbiome (GM), with the ability to communicate with the brain bidirectionally through the microbiome-gut-brain axis, has attracted much attention in AD-related studies, owing to their strong associations with amyloids, systematic and focal inflammation, impairment of vascular homeostasis and gut barrier, mitochondrial dysfunction, etc., making the regulation of GM, specifically supplementation of probiotics a promising candidate for AD treatment. This article aims to review the leading-edge knowledge concerning potential roles of GM in AD pathogenesis and of probiotics in its treatment and prevention.

Machine Learning of Serum Metabolic Patterns Encodes Asymptomatic SARS-CoV-2 Infection.

Asymptomatic COVID-19 has become one of the biggest challenges for controlling the spread of the SARS-CoV-2. Diagnosis of asymptomatic COVID-19 mainly depends on quantitative reverse transcription PCR (qRT-PCR), which is typically time-consuming and requires expensive reagents. The application is limited in countries that lack sufficient resources to handle large-scale assay during the COVID-19 outbreak. Here, we demonstrated a new approach to detect the asymptomatic SARS-CoV-2 infection using serum metabolic patterns combined with ensemble learning. The direct patterns of metabolites and lipids were extracted by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) within 1 s with simple sample preparation. A new ensemble learning model was developed using stacking strategy with a new voting algorithm. This approach was validated in a large cohort of 274 samples (92 asymptomatic COVID-19 and 182 healthy control), and provided the high accuracy of 93.4%, with only 5% false negative and 7% false positive rates. We also identified a biomarker panel of ten metabolites and lipids, as well as the altered metabolic pathways during asymptomatic SARS-CoV-2 Infection. The proposed rapid and low-cost approach holds promise to apply in the large-scale asymptomatic COVID-19 screening.

Black mulberry ethanol extract attenuates atherosclerosis-related inflammatory factors and downregulates PPARγ and CD36 genes in experimental atherosclerotic rats.

Atherosclerosis (AS) is the pathological basis of various vascular diseases and currently is seriously affecting human health. Numerous studies have paid more attention to natural medicines with anti-AS properties. As a traditional Uygur folk medicine, black mulberry fruits are conventionally used in the prevention and treatment of cardiovascular diseases in southern Xinjiang of China, and their underlying mechanisms remain unknown. Our previous study revealed that the ethanol extract of black mulberry (EEBM) inhibited AS development by improving lipid metabolism abnormalities, enhancing anti-oxidative activities, and reducing atherosclerotic lesions of atherosclerotic rats. Based on this, our objective was to further investigate the effects of EEBM on the expression of AS-related inflammatory factors and the key genes PPARγ and CD36 of the ox-LDL-PPARγ-CD36 feed-forward cycle in experimental atherosclerotic rats. Black mulberry fruits were extracted with acid ethanol and chromatographed on an AB-8 macroporous resin to obtain EEBM. All experimental rats were randomly divided into five groups: normal, model, model plus simvastatin (5 mg/kg d·body weight), and model plus low-dose and high-dose EEBM groups (105 and 210 mg/kg d·body weight, respectively). Serum levels of the inflammatory factors were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression of PPARγ and CD36 in atherosclerotic rats' liver tissue and thoracic aorta were determined by Q-PCR and western blot analysis, respectively. EEBM at high dose effectively attenuated the abnormally expressed AS-related inflammatory factors of TNF-α, IL-6, MMP-9, and CRP in atherosclerotic rats by 41.5%, 66.1%, 77.5%, and 79.5%, respectively. After treatment with high dose EEBM, the elevated-expressions of PPARγ and CD36 at the mRNA and protein levels in atherosclerotic rats were found to be obviously downregulated at both levels. These results demonstrate that EEBM might lessen the AS-related inflammatory reaction, and then inhibit the formation of ox-LDL, consequently downregulating the expression of PPARγ and CD36 at the mRNA and protein levels, thus reducing macrophage-foam-cell formation and prohibiting the development of atherosclerotic plaque through the ox-LDL-PPARγ-CD36 feed-forward cycle, which can effectively prevent the occurrence and development of AS in atherosclerotic rats.

Upregulation of DAB2IP Inhibits Ras Activity and Tumorigenesis in Human Pancreatic Cancer Cells.

KRAS mutation-induced Ras activation plays an important role in the pathogenesis of pancreatic cancer, but the role of wild-type Ras and Ras GTPase-activating proteins remains unclear. The present study was designed to determine the expression spectra of Ras GTPase-activating proteins genes in pancreatic cancer cells, and the role of DAB2IP, a Ras GTPase-activating proteins gene, in the development and progression of pancreatic cancer. Following the analyses of the expression profiles of 16 Ras GTPase-activating proteins in 6 pancreatic cancer cell lines including Bxpc-3 (with wild-type KRAS), Capan-2, Sw1990, Aspc-1, CFPAC-1, and Panc-1 (with mutant KRAS) and 1 normal human pancreatic ductal epithelial cell line, H6C7, the expression of DAB2IP messenger RNA was further analyzed by quantitative real-time polymerase chain reaction. The role of DAB2IP in pancreatic cancer was further investigated in vitro and in vivo by upregulating DAB2IP in Bxpc-3 cells through transfection of DAB2IP into Bxpc-3 cells with recombinant lentivirus. The DAB2IP expression in pancreatic cancer cells and tissues with wild-type KRAS was significantly lower than that in cells and tissues with mutant KRAS (P < .05). In Bxpc-3 cells with wild-type KRAS, overexpression of DAB2IP decreased the expression of P-AKT and P-ERK and the Ras activity; increased the expression of P-JNK and caspase 3; inhibited cell proliferation, invasiveness, and migration; and increased the cell sensitivity to cetuximab. Overexpression of DAB2IP inhibited tumor progression in a mouse model. In conclusion, DAB2IP downregulates Ras activity in wild-type pancreatic cancer cells. Overexpression of DAB2IP decreases the Ras activity, inhibits cell proliferation, and increases sensitivity to cetuximab in wild-type pancreatic cancer cells. In conclusion, DAB2IP may serve as a potential molecular therapeutic target for the treatment of pancreatic cancer.

High serum concentration of selenium, but not calcium, cobalt, copper, iron, and magnesium, increased the risk of both hyperglycemia and dyslipidemia in adults: A health examination center based cross-sectional study.

BACKGROUND: Metabolic disorders of glucose and lipid were associated with some mineral elements, and data were warranted from various contexts to make the association more explicit. OBJECTIVE: To investigate the relationships between the serum concentrations of six mineral elements (calcium, cobalt, copper, iron, magnesium, and selenium) and the risk of hyperglycemia and dyslipidemia in adults. METHODS: The basic information and the over-night fasting serum samples of adults were randomly collected at a health examination center. The serum concentrations of glucose and lipids were measured with an automatic biochemical analyzer, and the mineral elements were measured with an inductively coupled plasma mass spectrometer. Data were analyzed between the hyperglycemia group (HGg) and the normal glucose group (NGg) as well as between the dyslipidemia group (DLg) and the normal lipid group (NLg). RESULTS: A total of 1466 adults aged 22-81 years (male/female = 1.8) were included, 110 in the HGg and 1356 in the NGg, or 873 in the DLg and 593 in the NLg. The serum element concentration medians [P50 (P25-P75)] significantly different between the HGg and the NGg were 0.83 (0.75-0.94) vs. 0.76 (0.68-0.87) mg/L for copper and 100 (90-110) vs. 94 (87-103) µg/L for selenium (P < 0.001), while those between the DLg and the NLg were 99 (92-110) vs. 97 (90-106) mg/L for calcium, 0.78 (0.69-0.88) vs. 0.75 (0.66-0.85) mg/L for copper, 1.7 (1.4-2.0) vs. 1.6 (1.3-2.0) mg/L for iron, 24 (22-28) vs. 23 (22-27) mg/L for magnesium, and 97 (89-106) vs. 92 (84-100) µg/L for selenium (P < 0.05). When the copper and selenium between the HGg and the NGg were analyzed by logistic regression with age, gender, body mass index, and mineral elements adjusted, only the highest quartile of selenium concentration had association with the increased risk of hyperglycemia [quartile (Q) 4 against Q1: OR = 2.9, 95 % CI = 1.5-5.5, P < 0.001). When the five differed mineral elements between the DLg and the NLg were similarly analyzed, only iron and selenium had associations with the increased risk of dyslipidemia (e.g., Q4 against Q1: OR = 1.4, 95 % CI = 1.1-2.0 for iron and OR = 2.9, 95 % CI = 2.1-4.0 for selenium, P < 0.05). CONCLUSION: In contrast to those of calcium, cobalt, copper, iron, and magnesium, the higher serum concentration of selenium increased the risk of both hyperglycemia and dyslipidemia in the study population of adult Chinese.

Application of Lactobacillus as Adjunct Cultures in Wheat Dough Fermentation.

The purpose of this study was to evaluate the potential use of Lactobacillus from traditional Chinese sourdoughs of different regions as original adjunct cultures in the steamed bread making process. The effects of Lactobacillus on dough and steamed bread were evaluated. Some differences were obtained in the parameters of fermented dough (organic acid content, rheofermentative parameters, pH, and total titratable acidity [TTA]) and steamed bread (hardness, specific volume, organic acid content, shape, color, pH, TTA and sensory score) made with five different Lactobacillus strains (Pediococcus pentosaceus, Lactobacillus fermentum, Weissella confusa, Lactobacillus crustorum, and Pediococcus acidilactici). Steamed bread made with P. pentosaceus showed a significant increase in specific volume (from 2.19 to 2.41) and a decrease in hardness (from 3,158 g to 2,301 g). Dough leavened by L. fermentum showed significantly higher amounts of lactic acid and acetic acid than dough inoculated with W. confusa, which had values similar to those of the control. The dough fermented by P. pentosaceus exhibited the most gas production (1,811 mL), which is an important index of streamed bread quality. Our research provides a reference for making steamed bread with Lactobacillus. PRACTICAL APPLICATION: Probiotic Lactobacillus is widely used to produce fermenting foods and has been used in bread processing to improve the quality and characteristics of bread. Steamed bread is one of the most popular fermented foods in northern China. However, there is little information about the application of Lactobacillus in Chinese steamed bread. This study explored the potential use of Lactobacillus to improve the characteristics and quality of steamed bread.

Long Noncoding RNA PRRG4-4 Promotes Viability, Cell Cycle, Migration, and Invasion in Lung Cancer Cells.

There is a perception that long noncoding RNA (lncRNA) has relationship with carcinogenesis. Many studies have previously identified and validated that the section of chromosome 11p13 is associated with high incidence of tumor. In this study, we investigated a new lncRNA, named lncPRRG4-4, mapped to 11p13 and suspected that lncPRRG4-4 was a potential lung cancer-related gene. To explore its role in carcinogenesis, we first demonstrated that lncPRRG4-4 was upregulated in lung cancer tissues compared with adjacent nontumor tissues and functioned as an oncogene in lung cancer cells. The lncPRRG4-4 was significantly upregulated in lung cancer tissues compared with adjacent normal counterparts (mean ± standard deviation: 0.12 ± 0.84 vs. 0.05 ± 0.22; p < 0.001). Patients with metastasis exhibited high levels of lncPRRG4-4 expression than those without metastasis in both the southern samples (p = 0.045) and eastern samples (p = 0.030), total samples (p = 0.004). In addition, downregulation of lncPRRG4-4 expression inhibited lung cancer proliferation, viability, migration, and invasion ability, arrested cell cycle, facilitated apoptosis, and vice versa. Taken together, these observations suggested that the lncPRRG4-4 functions as an oncogene in lung cancer cells.

Unravelling cadmium toxicity and nitric oxide induced tolerance in Cucumis sativus: Insight into regulatory mechanisms using proteomics.

Nitric oxide (NO) is a signal molecule that can mediate a wide range of physiological processes against cadmium (Cd) toxicity in plants. However, little information can be used to reveal the global and systematic mitigative mechanism of NO in improving Cd stress tolerance of cucumber plants. In the present study, we used Isobaric Tag for Relative and Absolute Quantification (iTRAQ) analysis to identify 1691 proteins, which can be used to determine the role of NO in regulating the molecular changes of proteome in cucumber leaves exposed to Cd stress. Several dysregulated key proteins indicated that Cd-induced physiological deterioration of cucumber leaves were mainly involved in metabolic process, cellular process, response to stimulus and so on. Metabolic pathway analysis indicated that several Cd-disruptive pathways were markedly reversed by NO treatments, including Cd transport and localization, photosynthesis, chlorophyll metabolism, redox homeostasis, glutathione-mediated Cd detoxification and Ca2+ signaling transduction. Taken together, this iTRAQ analysis provides more comprehensive insights into the physiological and molecular mechanisms of NO against Cd toxicity in cucumber plants.

Effects of the ethanol extract of black mulberry (Morus nigra L.) fruit on experimental atherosclerosis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis (AS) is the major pathogenic component of coronary artery and cardiovascular disease. Studies have increasingly focused on natural medicines that have lipid-lowering, anti-inflammatory, and endothelial-protection activities. Black mulberry fruits are traditionally used in Uyghur folk medicine for the prevention and treatment of cardiovascular diseases in southern Xinjiang region of China. However, its underlying mechanisms remain unknown. Thus, our objective was to explore the effects and underlying mechanisms of ethanol extract of black mulberry (EEBM) in experimental atherosclerotic rats. MATERIALS AND METHODS: The black mulberry fruit was extracted with acid ethanol and chromatographed on an AB-8 macroporous resin to obtain EEBM. Atherosclerotic rats were divided into five groups: normal, model, model plus simvastatin (5mg/kgd·body weight), and model plus low-dose and high-dose EEBM groups (105 and 210mg/kgd·body weight, respectively). Serum lipid profiles were measured by an automatic biochemistry analyser. The activities of anti-oxidative enzymes were determined using the chemical colorimetric method. Pathological changes in liver and arteries were examined by hematoxylin and eosin (H&E), and the intima-media thickness was measured. RESULTS: The high-dose EEBM group showed significantly reduced total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels, as well as atherogenic index. Furthermore, treatment with high-dose EEBM markedly decreased malondialdehyde content and enhanced anti-oxidative enzyme activities. Histopathological examination showed that EEBM attenuated hepatic steatosis and reduced intima-media thickness and arterial atherosclerotic lesions in atherosclerotic rats. These results suggest that EEBM suppressed atherosclerosis development in atherosclerotic rats by regulating lipid metabolism abnormalities, enhancing anti-oxidative activities, and reducing atherosclerotic lesions, which could be attributed to anthocyanins (23.75%), or the cooperative action of anthocyanins, polyphenols (2.95%), and flavonoids (0.94%).